Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer

Author:

Trinidad Camille1,Pathak Harsh1,Cheng Shibo2,Tzeng Shin-Cheng3,Madan Rashna1,Sardiu Mihaela1,Bantis Leonidas1,Deighan Clayton4,Jewell Andrea1,Zeng Yong2,Godwin Andrew1

Affiliation:

1. The University of Kansas Medical Center

2. University of Florida

3. The Donald Danforth Plant Science Center

4. NanoFCM

Abstract

Abstract High grade serous ovarian carcinoma (HGSOC) accounts for ~ 70% of ovarian cancer cases. Non-invasive, highly specific blood-based tests for pre-symptomatic screening in women are crucial to reducing the mortality associated with this disease. Since most HGSOCs typically arise from the fallopian tubes (FT), our biomarker search focused on proteins found on the surface of extracellular vesicles (EVs) released by both FT and HGSOC tissue explants and representative cell lines. Using mass spectrometry, 985 EV proteins (exo-proteins) were identified that comprised the FT/HGSOC EV core proteome. Transmembrane exo-proteins were prioritized because these could serve as antigens for capture and/or detection. With a nano-engineered microfluidic platform, six newly discovered exo-proteins (ACSL4, IGSF8, ITGA2, ITGA5, ITGB3, MYOF) plus a known HGSOC associated protein, FOLR1 exhibited classification performance ranging from 85–98% in a case-control study using plasma samples representative of early (including stage IA/B) and late stage (stage III) HGSOCs. Furthermore, by linear combination of IGSF8 and ITGA5 based on logistic regression analysis, we achieved a sensitivity of 80% (99.8% specificity). These lineage-associated exo-biomarkers have potential to detect cancer while localized to the FT when patient outcomes are more favorable.

Publisher

Research Square Platform LLC

Reference68 articles.

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